title: Cessation of epithelial Bmp signaling switches the differentiation of crown epithelia to the root lineage in a β-catenin-dependent manner.
abstract: The differentiation of dental epithelia into enamel-producing ameloblasts or the root epithelial lineage compartmentalizes teeth into crowns and roots. Bmp signaling has been linked to enamel formation, but its role in root epithelial lineage differentiation is unclear. Here we show that cessation of epithelial Bmp signaling by Bmpr1a depletion during the differentiation stage switched differentiation of crown epithelia into the root lineage and led to formation of ectopic cementum-like structures. This phenotype is related to the upregulation of Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT). Although epithelial β-catenin depletion during the differentiation stage also led to variable enamel defect and precocious/ectopic formation of fragmented root epithelia in some teeth, it did not cause ectopic cementogenesis and inhibited EMT in cultured dental epithelia. Concomitant epithelial β-catenin depletion rescued EMT and ectopic cementogenesis caused by Bmpr1a depletion. These data suggested that Bmp and Wnt/β-catenin pathways interact antagonistically in dental epithelia to regulate the root lineage differentiation and EMT. These findings will aid in the design of new strategies to promote functional differentiation in the regeneration and tissue engineering of teeth and will provide new insights into the dynamic interactions between the Bmp and Wnt/β-catenin pathways during cell fate decisions.
authors.affiliation: Institute for Regenerative Medicine at Scott & White Hospital, Molecular and Cellular Medicine Department, College of Medicine, Texas A&M Health Science Center, Houston, Texas, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Hai
authors.forename: Lizheng
authors.initials: L
authors.lastname: Qin
authors.forename: Xinyu
authors.initials: X
authors.lastname: Ti
authors.forename: Lei
authors.initials: L
authors.lastname: Shangguan
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lindsey
authors.initials: L
authors.lastname: Wiggins
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
authors.forename: Julia Yu Fong
authors.initials: JY
authors.lastname: Chang
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D025021:Cementogenesis; D003739:Dental Cementum / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D055786:Gene Knockout Techniques; D007180:Incisor / Q000002:abnormalities / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D019228:Tooth Crown / Q000166:cytology* / Q000502:physiology; D014092:Tooth Root / Q000166:cytology* / Q000502:physiology; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I